Phenotypes of Spinocerebellar Ataxia Type 6 and Familial Hemiplegic Migraine Caused by a Unique CACNA1A Missense Mutation in Patients From a Large Family

Abstract

The disease-causing mutation in this family was identified, showing that a unique mutation in the CACNA1A gene causes several phenotypes, including those of SCA6 and FHM, thus suggesting that SCA6 and FHM are not only allelic diseases but are the same disorder with a large phenotypic variability.

Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation

“…Chronic progressive cerebellar ataxia appeared after paroxysmal episodes (9 patients), in advance of these (5 patients), or as an isolated feature (11 patients); this confirms and adds robustness to descriptions of the variable natural history of ataxia in FHM type 1-related disorders. 5,18,19,23 The majority of our patients, however, did not have nystagmus, which disagrees with previous reports. One patient (III:14) with a long history of ataxia had normal findings on brain magnetic resonance imaging, which suggested that atrophic cerebellar degeneration is not a necessary pathological expression of channelopathies.…”

Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation

“…Chronic progressive cerebellar ataxia appeared after paroxysmal episodes (9 patients), in advance of these (5 patients), or as an isolated feature (11 patients); this confirms and adds robustness to descriptions of the variable natural history of ataxia in FHM type 1-related disorders. 5,18,19,23 The majority of our patients, however, did not have nystagmus, which disagrees with previous reports. One patient (III:14) with a long history of ataxia had normal findings on brain magnetic resonance imaging, which suggested that atrophic cerebellar degeneration is not a necessary pathological expression of channelopathies.…”

R583Q CACNA1A variant in SHM1 and ataxia: case report and literature update

“…Second, in most cases cerebellar signs are progressive and permanent making the phenotype of p.Arg583Gln mutations more similar to SCA6 than EA2. Lastly, except for a few cases in which migraine was triggered by fever or head trauma, in most cases, a provoking event was not detectable [5, 7]. Our case, except for relatively small attack duration, does not differ from other literature observations.…”

Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

“…This prevalent mutation has been previously identified in FHM families and in sporadic patients (Battistini et al 1999;Ducros et al 2001;Terwindt et al 2002;Alonso et al 2003;Thomsen et al 2007;Riant et al 2010a). In family #A00_100, only the proband presents HM (Fig.…”

Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation

“…Chronic progressive cerebellar ataxia appeared after paroxysmal episodes (9 patients), in advance of these (5 patients), or as an isolated feature (11 patients); this confirms and adds robustness to descriptions of the variable natural history of ataxia in FHM type 1-related disorders. 5,18,19,23 The majority of our patients, however, did not have nystagmus, which disagrees with previous reports. One patient (III:14) with a long history of ataxia had normal findings on brain magnetic resonance imaging, which suggested that atrophic cerebellar degeneration is not a necessary pathological expression of channelopathies.…”

R583Q CACNA1A variant in SHM1 and ataxia: case report and literature update

“…Second, in most cases cerebellar signs are progressive and permanent making the phenotype of p.Arg583Gln mutations more similar to SCA6 than EA2. Lastly, except for a few cases in which migraine was triggered by fever or head trauma, in most cases, a provoking event was not detectable [5, 7]. Our case, except for relatively small attack duration, does not differ from other literature observations.…”

Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

“…This prevalent mutation has been previously identified in FHM families and in sporadic patients (Battistini et al 1999;Ducros et al 2001;Terwindt et al 2002;Alonso et al 2003;Thomsen et al 2007;Riant et al 2010a). In family #A00_100, only the proband presents HM (Fig.…”

Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation

“…Chronic progressive cerebellar ataxia appeared after paroxysmal episodes (9 patients), in advance of these (5 patients), or as an isolated feature (11 patients); this confirms and adds robustness to descriptions of the variable natural history of ataxia in FHM type 1-related disorders. 5,18,19,23 The majority of our patients, however, did not have nystagmus, which disagrees with previous reports. One patient (III:14) with a long history of ataxia had normal findings on brain magnetic resonance imaging, which suggested that atrophic cerebellar degeneration is not a necessary pathological expression of channelopathies.…”

R583Q CACNA1A variant in SHM1 and ataxia: case report and literature update

“…Second, in most cases cerebellar signs are progressive and permanent making the phenotype of p.Arg583Gln mutations more similar to SCA6 than EA2. Lastly, except for a few cases in which migraine was triggered by fever or head trauma, in most cases, a provoking event was not detectable [5, 7]. Our case, except for relatively small attack duration, does not differ from other literature observations.…”

Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

“…This prevalent mutation has been previously identified in FHM families and in sporadic patients (Battistini et al 1999;Ducros et al 2001;Terwindt et al 2002;Alonso et al 2003;Thomsen et al 2007;Riant et al 2010a). In family #A00_100, only the proband presents HM (Fig.…”